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1.
Exp Brain Res ; 242(1): 33-45, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37932484

RESUMO

Spontaneous subarachnoid hemorrhage (SAH) accounts for approximately 5% of all cases of stroke. SAH is correlated with elevated rates of mortality and disability. Despite significant advancements in comprehending the pathogenesis and surgical management, efficacious clinical interventions remain restricted, and the prognosis is yet to be enhanced. MicroRNAs play a crucial role in various pathological processes in organisms. Revealing these regulatory processes is conducive to the development of new treatment methods. MicroRNA-124 is highly expressed in the nervous system and has significant research value for SAH. This study aims to explore the role of miR-124 in the early post-SAH period on neural function and verify whether it is involved in the pathological and physiological processes of SAH. In this study, we used methods such as comparing the expression levels of miR-124 in cerebrospinal fluid, establishing a rat SAH model, and a mouse embryonic primary neuron hemoglobin stimulation model to verify the downstream proteins of miR-124 in SAH. Through transfection techniques, we adjusted the expression of this small RNA in Vitro and in Vivo models using miR-124 inhibitor and mimic in the primary neuron hemoglobin stimulation model and rat SAH model, and observed the phenotype. Finally, by consulting the literature and verifying in Vivo and in Vitro methods, AK4 and downstream molecule ATF3 were identified as downstream targets of miR-124.


Assuntos
MicroRNAs , Fármacos Neuroprotetores , Hemorragia Subaracnóidea , Ratos , Animais , Camundongos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Hemorragia Subaracnóidea/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Hemoglobinas
2.
Cell Death Differ ; 30(9): 2104-2119, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37582865

RESUMO

Macrophages are usually educated to tumor-associated macrophages (TAMs) in cancer with pro-tumor functions by tumor microenvironment (TME) and TAM reprogramming has been proposed as a potential tumor immunotherapy strategy. We recently demonstrated the critical role of Zinc-fingers and homeoboxes 2 (Zhx2) in macrophages' metabolic programming. However, whether Zhx2 is responsible for macrophage polarization and TAMs reprogramming is largely unknown. Here, we show that Zhx2 controls macrophage polarization under the inflammatory stimulus and TME. Myeloid-specific deletion of Zhx2 suppresses LPS-induced proinflammatory polarization but promotes IL-4 and TME-induced anti-inflammatory and pro-tumoral phenotypes in murine liver tumor models. Factors in TME, especially lactate, markedly decrease the expression of Zhx2 in TAMs, leading to the switch of TAMs to pro-tumor phenotype and consequent cancer progression. Notably, reduced ZHX2 expression in TAM correlates with poor survival of HCC patients. Mechanistic studies reveal that Zhx2 associates with NF-κB p65 and binds to the Irf1 promoter, leading to transcriptional activation of Irf1 in macrophages. Zhx2 functions in maintaining macrophage polarization by regulating Irf1 transcription, which may be a potential target for macrophage-based cancer immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Regulação da Expressão Gênica , Neoplasias Hepáticas/patologia , Macrófagos/metabolismo , Fatores de Transcrição/metabolismo , Microambiente Tumoral
3.
Mol Carcinog ; 62(9): 1295-1311, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37212496

RESUMO

TMEM147 was identified as a core component of ribosome-bound translocon complex at ER/NE. So far, sparse studies reported its expression profiling and oncological implications in hepatocellular carcinoma (HCC) patients. Here we inspected TMEM147 expression levels in HCC cohorts from public databases and tumor tissues. TMEM147 was augmented at transcriptional levels (p < 0.001) and protein levels in HCC patients. A series of bioinformatics tools implemented in R studio were orchestrated in TCGA-LIHC to evaluate the prognostic significance, compile relevant gene clusters, and explore the oncological functions and therapy responses. It is suggested that TMEM147 could predict poor clinical outcomes effectively and independently (p < 0.001, HR = 2.231 for overall survival (OS) vs. p = 0.04, HR = 2.296 for disease-specific survival), and was related to risk factors including advanced histologic tumor grade (p < 0.001), AFP level (p < 0.001) and vascular invasion (p = 0.007). Functional enrichment analyses indicated that TMEM147 was involved in cell cycle, WNT/MAPK signaling pathways and ferroptosis. Expression profiling in HCC cell lines, mouse model, and a clinical trial revealed that TMEM147 was a considerable target and marker for adjuvant therapy in vitro and in vivo. Subsequentially, in vitro wet-lab experimentation authenticated that TMEM147 would be downregulated by Sorafenib administration in hepatoma cells. Lentivirus-mediated overexpression of TMEM147 could promote cell cycle progression from S phase into G2/M phase, and enhance cell proliferation, thus attenuating drug efficacy and sensitivity of Sorafenib. Further explorations into TMEM147 may inspire a fresh perspective to predict clinical outcomes and improve therapeutic efficacy for HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Ciclo Celular , Divisão Celular , Linhagem Celular Tumoral
4.
Pathol Res Pract ; 245: 154460, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37116368

RESUMO

BACKGROUND: As most common primary tumor in adult's brain, the glioblastoma (GBM) still ends up with poor survival period. Little progress has been made in recent decades in terms of improving prognosis. There's still an urgent need for novel targets and strategies to overcome such malignancy. METHODS: Both the Cancer Genome Atlas and Gene Expression Omnibus databases were used to analyze expression differences and correlations. The immunohistochemistry and survival analysis were used to verify expression differences. Tumorigenesis was assessed using cholecystokinin and the orthotopic xenograft model. Metastasis was determined by the transwell assay and the tail vein xenograft model. RESULTS: Inhibin subunit beta B (INHBB) was upregulated in GBM and predicted poor survival. It promoted tumor growth, invasion and stemness in GBM. INHBB expression correlated with the epidermal growth factor receptor (EGFR) expression and downstream AKT and ERK expression levels. The increased tumor progression induced by INHBB could be inhibited by afatinib. CONCLUSION: This study revealed INHBB as a tumor progression and independent prognostic factor in GBM, which could be a potential upper stream molecular of EGFR/ERK/AKT signaling.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Subunidades beta de Inibinas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Animais , Células-Tronco Neoplásicas
5.
Br J Neurosurg ; 37(4): 800-802, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31535577

RESUMO

We report an intractable post cranioplasty hematoma which required multiple operations. The titanium cranioplasty was for a cranial defect from surgery for an intracranial hemorrhage. Despite removal of the cranioplasty the haematoma repeatedly recurred. So we applied the cryohemostasis by the ice packs 4 times a day for 30 minutes. With this simple cooling method haemostasis was achieved.


Assuntos
Procedimentos de Cirurgia Plástica , Couro Cabeludo , Humanos , Couro Cabeludo/cirurgia , Crânio/cirurgia , Craniotomia/efeitos adversos , Hematoma/etiologia , Hematoma/cirurgia , Titânio , Estudos Retrospectivos , Complicações Pós-Operatórias/cirurgia
6.
Artigo em Inglês | MEDLINE | ID: mdl-36429993

RESUMO

Along with the increasing number of prefabricated buildings being constructed in China each year, the incident rate of hoisting operations has been continuously rising. In order to improve construction safety in hoisting operations of prefabricated buildings, this paper analyzes the construction workers' unsafe behaviors using the Hazard and Operability (HAZOP) method. A questionnaire survey and a literature review were first performed to gather information on safety risks and influencing factors during each stage of hoisting operations, and the survey results were statistically analyzed using the SPSS software. Next, HAZOP was applied to identify the deviation and change of the unsafe behaviors as well as their causes, consequences, and countermeasures. Finally, a case study was presented to verify the effectiveness of the countermeasures through a comparison and evaluation method from experimental economics. This paper demonstrates the use of HAZOP to analyze construction workers' unsafe behaviors in hoisting operations of prefabricated buildings, and effective countermeasures in each stage of hoisting operations are proposed to mitigate unsafe behaviors. This paper therefore provides an innovative method and a theoretical foundation for reducing unsafe behaviors in hoisting operations of prefabricated buildings and serves as a reference for decision-making for hoisting safety policies in prefabricated construction projects.


Assuntos
Indústria da Construção , Humanos , Inquéritos e Questionários , China
7.
J Oncol ; 2021: 5538911, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188681

RESUMO

TIPE1, a newly identified member in TIPE (TNFAIP8) family, plays an important role in tumorigenesis and immune regulation, but its role in ovarian cancer, especially in tumor metastasis, remains unknown. In the current study, we aimed to reveal the protein expression spectrum of TIPE1 in normal human tissues and explored its relationship with metastasis in ovarian cancer. The results of IHC staining showed that TIPE1 protein was not only detected in cytoplasm in most human tissues but also expressed in both cytoplasm and nucleus in squamous epithelium and some epithelial-derived cells with secretory functions, such as esophagus, cervix uteri and ovary, and thyroid gland. Moreover, TIPE1 protein was downregulated in ovarian cancer tissues compared with that in the paracancerous. More importantly, TIPE1 suppressed tumorigenesis and metastasis of ovarian cancer in vitro and in vivo, as evidence shows its ability to suppress growth, colony formation, migration, and epithelial-mesenchymal transition (EMT) of ovarian cancer. Taken together, our results demonstrate the suppressor role of TIPE1 in ovarian cancer metastasis, indicating TIPE1 might be a metastasis predictor and a novel therapeutic target for ovarian cancer.

8.
PLoS One ; 16(4): e0248329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33857162

RESUMO

The elderly usually suffer from many diseases. Improving the quality of life of the elderly is an urgent social issue. In this present study, D-galactose treated aging mice models were used to reveal the effects of different animal sources and different doses of whey protein (WP) on the immune indexes organs and intestinal flora. A total of 9 groups were set up, including normal control (NC), negative control (NS), positive control (Vc), low-, medium- and high-doses of cow WP intervention groups (CL, CM and CH for short, correspondingly) and low-, medium- and high-doses of goat WP intervention groups (GL, GM and GH for short, correspondingly). The body weight gain, thymus/body weight ratio, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, spleen immunoglobulins G (IgG), spleen interleukin-2 (IL-2) and spleen interleukin-2 (IL-6) were measured. Then, the intestinal contents were collected, and 16s genes of intestinal bacteria were sequenced to reveal the changes in bacterial flora structure. WP intervention significantly increased the weight gain, thymus/body ratio and SOD activity, but decrease the content of MDA. WP intervention increased some immune indicators. All the WP treated aging mice showed similar values of physiological indexes to that of the Vc group, even better. The relative abundance of Lactobacillus and Stenotrophomonas was increased and decreased, respectively, by both cow and goat WP. Lactobacillus may be involved in regulating the functional repair of organisms. In contrast, Stenotrophomonas might play a negative role in the immune and antioxidant capacity of the body. Combining physiological indicators and intestinal flora structure, low-concentration WP for cow and goat might be optimal for aging models.


Assuntos
Envelhecimento/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Proteínas do Soro do Leite/farmacologia , Animais , Antioxidantes/metabolismo , Modelos Animais de Doenças , Feminino , Galactose/metabolismo , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Qualidade de Vida , Baço/metabolismo , Superóxido Dismutase/metabolismo , Proteínas do Soro do Leite/metabolismo
9.
Food Sci Nutr ; 8(6): 2798-2808, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32566197

RESUMO

Chicken plasma protein hydrolysate (CPPH) was prepared by trypsin with angiotensin I-converting enzyme (ACE) inhibitory activity of 53.5% ± 0.14% and the degree of hydrolysis (DH) of 16.22% ± 0.21% at 1 mg·ml-1; then, five proteases, including pepsin, trypsin, papain, alcalase, and neutrase, were employed to improve ACE inhibitory ability by catalyzing plastein reaction. The results indicated that trypsin-catalyzed plastein reaction showed the highest ACE inhibitory activity. The exogenous amino acids of leucine, histidine, tyrosine, valine, and cysteine were selected to modify the CPPH. The leucine-modified plastein reaction released the highest ACE inhibitory activity. The effects of four reaction parameters on plastein reaction were studied, and the optimal conditions with the purpose of obtaining the most powerful ACE inhibitory peptides from modified products were obtained by response surface methodology (RSM). The maximum ACE inhibition rate of the modified hydrolysate reached 82.07% ± 0.03% prepared at concentration of hydrolysates of 30%, reaction time of 4.9 hr, pH value of 8.0, temperature of 40°C, and E/S ratio of 5,681.62 U·g-1. The results indicated that trypsin-catalyzed plastein reaction increased ACE inhibitory activity of chicken plasma protein hydrolysates by 28.57%.

10.
Cell Death Differ ; 27(5): 1693-1708, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31740790

RESUMO

Non-alcoholic fatty liver disease (NAFLD) leads to hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. Here, we investigated the role of the tumor suppressor Zinc fingers and homeoboxes 2 (ZHX2) in the progression of NAFLD to HCC. ZHX2 expression was significantly decreased in fatty liver tissues, especially in the liver with NAFLD-HCC. ZHX2 overexpression disturbed lipid homeostasis of cultured HCC cells, and inhibited lipid deposition in hepatocytes both in vitro and in vivo. Moreover, ZHX2 inhibited uptake of exogenous lipids through transcriptional suppression of lipid lipase (LPL), leading to retarded proliferation of HCC cells. Importantly, LPL overexpression significantly reversed ZHX2-mediated inhibition of HCC cell proliferation, xenograft tumor growth, lipid deposition, and spontaneous liver tumor formation. Consistently, IHC staining demonstrated a negative correlation of ZHX2 with LPL in an HCC cohort. Collectively, ZHX2 protects hepatocytes from abnormal lipid deposition in NAFLD through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD-HCC progression. These findings illustrate a novel mechanism of NAFLD progression into HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Progressão da Doença , Proteínas de Homeodomínio/metabolismo , Lipídeos/química , Lipase Lipoproteica/metabolismo , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Fatores de Transcrição/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Fígado Gorduroso/metabolismo , Hepatócitos/metabolismo , Proteínas de Homeodomínio/genética , Humanos , Lipase Lipoproteica/genética , Neoplasias Hepáticas/genética , Hepatopatia Gordurosa não Alcoólica/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica , Fatores de Transcrição/genética , Transcrição Gênica
11.
Oncol Lett ; 18(6): 6614-6620, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788118

RESUMO

The recurrence and metastasis of hepatocellular carcinoma (HCC) are a major concern in current research. Epithelial-mesenchymal transition (EMT) is the leading cause underlying the high mobility and invasiveness of tumor cells. Myricetin is a natural flavonol with various pharmacological activities. The effects of myricetin on the migration and invasion of HCC MHCC97H cells were evaluated in the present study. Wound healing, Transwell migration and invasion assays were used to examine cell migration and invasion. Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to examine the expression of epithelial (E)-cadherin, neural (N)-cadherin and vimentin. The present study aimed to investigate the effects of myricetin on the migration and invasion of HCC MHCC97H cells. It was indicated that myricetin decreased the viability of MHCC97H cells in a concentration and time-dependent manner, and inhibited MHCC97H cells migration and invasion. As the concentration of myricetin increased, filopodia and lamellipodia in cells weakened and cells were arranged more closely. RT-qPCR and western blotting revealed that myricetin upregulated E-cadherin expression and downregulated N-cadherin. Collectively, the results of the present study demonstrate that myricetin may inhibit the migration and invasion of HCC MHCC97H cells by inhibiting the EMT process.

12.
Thorac Cancer ; 10(10): 1973-1983, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31441578

RESUMO

BACKGROUND: Both quantitative and qualitative aspects of plasma cell-free DNA (plasma cfDNA, pcfDNA) have been well-studied as potential biomarkers in non-small cell lung cancer (NSCLC). Accumulating evidence has proven that saliva also has the potential for the detection and analysis of circulating free DNA (saliva cfDNA, scfDNA). METHODS: In the current study, we aimed to explore the potential application of scfDNA in NSCLC diagnostics and consistency of epidermal growth factor receptor (EGFR) mutation detection in paired pcfDNA and scfDNA using droplet digital PCR (ddPCR) and analyze the relationship between EGFR mutations and clinical treatment response. RESULTS: In the quantitative cohort study, scfDNA concentration in NSCLC patients was no different from that in healthy donors, or in benign patients. ScfDNA concentration was significantly lower than pcfDNA concentration, yet they were not statistically significant in relevance (Spearman's rank correlation r = -0.123, P = 0.269). In the qualitative cohort study, the overall concordance rate of EGFR mutations between pcfDNA and scfDNA was 83.78% (31 of 37; k = 0.602; P < 0.001). EGFR mutation detection in paired pcfDNA and scfDNA was significantly correlated with the clinical treatment response (Spearman's rank correlation r = 0.664, P = 0.002). CONCLUSIONS: Our results demonstrated that saliva might not be the idea material for a cfDNA quantitative test, and scfDNA concentration is not applicable for NSCLC diagnostics. Conversely, scfDNA was capable of acting as the supplement for EGFR mutations due to the coincidence rate of EGFR mutation detection between scfDNA and pcfDNA.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , Ácidos Nucleicos Livres , Neoplasias Pulmonares/genética , Mutação , Saliva/metabolismo , Adulto , Idoso , Receptores ErbB/genética , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sensibilidade e Especificidade , Deleção de Sequência
13.
Onco Targets Ther ; 12: 3661-3670, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190868

RESUMO

Background/Aims: Recently, the insulin-like growth factor mRNA-binding protein 3 (IMP3) has been reported to be involved in tumorigenesis. We aimed to study the expression and role of IMP3 in human glioblastoma. Methods: We analyzed the expression of IMP3 in 70 cases of glioma tissues, normal brain tissues and 5 kinds of cell lines using western blot. Immunohistochemistry (IHC) was used to evaluate the expression and distribution of IMP3 in glioma tissues. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of IMP3 in vitro and in vivo. The epithelial-mesenchymal transition (EMT)-related biomarkers were detected by western blot. Results: We found that the expression level of IMP3 was obviously higher in glioma tissues than that in normal brain tissues, and associated with glioma grade. In-vitro assays revealed that IMP3 overexpression significantly induced cell proliferation, migration, and invasion. Mechanically, IMP3 over-expression downregulated the expression of E-cadherin, but upregulated the expressions of N-cadherin, vimentin, snail, slug and MMP9. However, the inhibition of IMP3 impaired these oncogenic effects. In vivo assay also demonstrated that silencing of IMP3 inhibited tumor growth and improved survival of tumor-bearing xenograft nude mice. Conclusion: IMP3 can promote cell proliferation, migration and invasion by inducing EMT in glioblastoma. Thus, targeting IMP3 pathway may be a novel way to treat patients with glioblastoma.

14.
Oncol Res ; 27(8): 911-921, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30982493

RESUMO

To date, miR-148-3p and DNMT1-recombinant human runt-related transcription factor 3 (RUNX3) axis have been linked to cell proliferation, migration, and invasion; however, their roles and relationships in human glioblastoma multiforme (GBM) are still not clear. Here we found that the expression of miR-148-3p in glioma tissues was decreased compared with adjacent nontumor tissues and correlated with WHO grade, tumor size, and prognosis as well as DNMT1 and RUNX3 expressions. Compared with NHA cells, the expression of miR-148-3p in U87 and U251 cells was also downregulated and accompanied with upregulation of DNMT1 and hypermethylation level of RUNX3 promoter region. miR-148-3p overexpression induced apoptosis and cell cycle arrest of U87 and U251 cells, and affected cell migration and invasion. miR-148-3p mimics effectively suppressed the expression of DNMT1 and methylation of RUNX3 promoter, finally upregulating RUNX3 expression. Mechanistically, the 3'-untranslated region (3'-UTR) of DNMT1 was a direct target of miR-148-3p. Overexpression of miR-148-3p or inhibition of DNMT1 induced the expression of E-cadherin and reduced the expressions of N-cadherin, vimentin, MMP-2, and MMP-9. In conclusion, miR-148-3p directly repressed the expression of DNMT1 and inhibited proliferation, migration, and invasion by regulating DNMT1-RUNX3 axis and the epithelial-mesenchymal transition in GBM. Our findings provide a new foundation for treatment of patients with GBM.


Assuntos
Subunidade alfa 3 de Fator de Ligação ao Core/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , Glioblastoma/genética , MicroRNAs/genética , Adulto , Idoso , Apoptose/genética , Movimento Celular/genética , Proliferação de Células/genética , Metilação de DNA/genética , Intervalo Livre de Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Glioblastoma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico
15.
Lab Invest ; 98(7): 935-946, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29497175

RESUMO

Genotype-directed targeted therapy has become one of the standard treatment options for non-small cell lung cancer (NSCLC). There have been numerous limitations associated with mutation analysis of tissue samples. Consequently, mutational profile analysis of circulating cell-free DNA (cfDNA) by highly sensitive droplet digital PCR (ddPCR) assay has been developed. Possibly due to differences in cfDNA concentrations, previous studies have shown numerous discrepancies in mutation detection consistency between tissue and cfDNA. In order to rigorously analyze the amount of cfDNA needed, we constructed 72 athymic nude mice xenografted with NCI-H1975 (harboring a EGFR T790M mutation) or NCI-H460 (harboring a KRAS Q61H mutation) human NSCLC. We thoroughly investigated the relationship between plasma cfDNA using Q-PCR targeting human long interspersed nuclear element-1 (LINE-1) retrotransposon and the mouse ACTB gene, and the accuracy of mutation detection by ddPCR at different times post-graft. Our results show that the concentration and fragmentation of human (tumor) derived cfDNA (hctDNA) were positively correlated with tumor weight, but not with mouse-derived cfDNA (mcfDNA). Quantification of cfDNA by Q-PCR depends on the amplified target length. Mutation copies in plasma of per milliliter were positively linked to tumor weight, hctDNA level and hctDNA/mcfDNA ratio, respectively. Furthermore, tumor weight, hctDNA level and ratio of hctDNA/mcfDNA were significantly higher in cfDNA mutation-positive mice than in negative mice. Also, our data indicate that when plasma hctDNA level and hctDNA/mcfDNA ratio reach a certain level in xenografted mice, plasma cfDNA mutation can be detected. In summary, the present study suggests that determination of ctDNA levels may be essential for reliable mutation detection by analysis of cfDNA.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/sangue , Neoplasias Pulmonares/genética , Mutação/genética , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , DNA Tumoral Circulante/genética , Análise Mutacional de DNA , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Neoplasias Experimentais , Reação em Cadeia da Polimerase
16.
Opt Express ; 26(3): 2794-2806, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29401815

RESUMO

Continuous-variable quantum key distribution (CVQKD) with a real local oscillator (LO) has been extensively studied recently due to its security and simplicity. In this paper, we propose a novel implementation of a high-key-rate CVQKD with a real LO. Particularly, with the help of the simultaneously generated reference pulse, the phase drift of the signal is tracked in real time and then compensated. By utilizing the time and polarization multiplexing techniques to isolate the reference pulse and controlling the intensity of it, not only the contamination from it is suppressed, but also a high accuracy of the phase compensation can be guaranteed. Besides, we employ homodyne detection on the signal to ensure the high quantum efficiency and heterodyne detection on the reference pulse to acquire the complete phase information of it. In order to suppress the excess noise, a theoretical noise model for our scheme is established. According to this model, the impact of the modulation variance and the intensity of the reference pulse are both analysed theoretically and then optimized according to the experimental data. By measuring the excess noise in the 25km optical fiber transmission system, a 3.14Mbps key rate in the asymptotic regime proves to be achievable. This work verifies the feasibility of the high-key-rate CVQKD with a real LO within the metropolitan area.

17.
Zhongguo Zhong Yao Za Zhi ; 42(24): 4864-4869, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29493159

RESUMO

To investigate the effects of isovitexin Ⅳ on transient outward potassium current in rat ventricular myocytes. In this study, MTT assay was used to investigate the safe range of isovitexin. The results showed that the IC50 of the drug was in the range of 10-30 µmol•L⁻¹, and the drug concentration of 1-3 µmol•L⁻¹ for the patch clamp test was within the safe range. In addition, the single ventricular myocytes were obtained by single-enzymatic hydrolysis through aortic retrograde perfusion. The transient outward potassium current (Ito) of rat ventricular myocytes was guided and measured by whole-cell patch-clamp technique and the changes of current characteristics were recorded after isovite was applied. When the concentration of IV was less than 0.1 µmol•L⁻¹, there was no significant effect on Ito. However, with the increase in the concentration of IV (≥0.3 µmol•L⁻¹), the peak of Ito was decreased gradually, from (32.32±2.9) pA/pF to (25.83±4.3) pA/pF, 1 µmol•L⁻¹ IV and (19.51±3.5) pA/pF, 3 µmol•L⁻¹ IV respectively, with an inhibition effect in a concentration-dependent manner. In the range of 1-3 µmol•L⁻¹, IV down-regulated the I-V curve of Ito significantly. The activation curve showed that IV can enable the maximum half activation potential (V1/2) to move to the positive direction, and the V1/2 was increased from (19.59±1.6) mV to (22.81±1.7) mV and (28.86±1.4) mV at concentration of 1, 3 µmol•L⁻¹, meanwhile the activation curve moved to the right. However, the maximum half inactivating potential (V1/2) of the steady-state inactivation curve of Ito was significantly decreased from (-51.43±0.99) mV to (-61.81±1.3) mV with concentration of 1 µmol•L⁻¹ and (-71.50±1.4) mV with concentration of 3 µmol•L⁻¹. The inactivation time constant of recovery from inactivation (τ) was up-regulated significantly from (94.89±0.73) ms to (118.5±1.5) ms and (162.4±1.4) ms at concentration of 1, 3 µmol•L⁻¹ respectively. Meanwhile IV could enable the inactivation recovery curve to move to the right, which suggested that it can prolong the recovery time from inactivation of the transient outward potassium channel. In conclusion, isovitexin had a high inhibitory effect on Ito in rat ventricular myocytes.


Assuntos
Apigenina/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Canais de Potássio/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo , Animais , Ventrículos do Coração/citologia , Técnicas de Patch-Clamp , Ratos
18.
Lab Invest ; 96(11): 1189-1197, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27617399

RESUMO

Endotoxic shock is the primary cause of morbidity and mortality in hospital patients, creating an urgent need to explore the mechanisms involved in sepsis. Our previous studies showed that T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) attenuated the inflammatory response through regulating the functions of macrophages. However, the mechanism by which Tim-4 does this has not been fully elucidated. In this study, we found that Tim-4 expression was increased in lipopolysaccharide (LPS)-induced endotoxic shock. Interestingly, the survival rate of mice in the Tim-4 overexpression group was higher than that of the control group after LPS administration. To investigate the function of Tim-4 in LPS-induced inflammation, we further demonstrated that Tim-4 attenuated LPS-induced endotoxic shock by inhibiting cytokine production by macrophages. Blocking expression of Tim-4 and nuclear factor-kappa B (NF-κB) signal inhibition showed that Tim-4 inhibited cytokine production via NF-κB signaling pathway. This study indicates that Tim-4 may exert its immune modulation by regulating inflammatory factor secretion and might act as a novel potential target for inflammatory diseases, especially endotoxic shock.


Assuntos
Proteínas de Membrana/metabolismo , Choque Séptico/metabolismo , Animais , Linhagem Celular , Feminino , Interleucina-6/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Proteínas de Membrana/farmacologia , Proteínas de Membrana/uso terapêutico , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Choque Séptico/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
19.
Phys Chem Chem Phys ; 18(32): 22661-7, 2016 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-27476928

RESUMO

Solid films are considered as typical model systems to study size effects on thermal vacancy concentration in nanomaterials. By combining the generalized Young-Laplace equation with the chemical potential of vacancies, a strict size-dependent thermodynamic model of vacancies, which includes the surface intrinsic elastic parameters of the eigenstress, Young's modulus and the geometric size of the solid films, was established. The vacancy concentration changes in the film with respect to the bulk value, depending on the geometric size and surface stress sign of the solid films. Atomistic simulations of Au and Pt films verified the developed thermodynamic model. These results provide physical insights into the size-dependent thermal vacancy concentration in nanomaterials.

20.
Sci Rep ; 6: 26897, 2016 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-27256492

RESUMO

Thermodynamic analysis and molecular dynamics simulations were conducted to systematically study the size-dependent electrochemical response of solids. By combining the generalized Young-Laplace equation with the popular Butler-Volmer formulation, the direct influence of surface stress on solid film electrochemical reactions was isolated. A series of thermodynamic formulas were developed to describe the size-dependent electrochemical properties of the solid surface. These formulas include intrinsic surface elastic parameters, such as surface eigenstress and surface elastic modulus. Metallic films of Au, Pt, Ni, Cu and Fe were studied as examples. The anodic current density of the metal film increased, while the equilibrium potential decreased with increasing solid film thickness.

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